Perspectives Commentary on: Comparison Between Surgical Resection and Stereotactic Radiosurgery in Patients with a Single Brain Metastasis from NoneSmall Cell Lung Cancer by Bougie et al. World Neurosurg 83:900-906, 2015
To Remove or Not to Remove, that Is the Question? Bruce E. Pollock1,2
B
rain metastasis from nonesmall cell lung cancer is likely the most common brain tumor in adults because of the high prevalence of this disease. For many years, wholebrain radiation therapy (WBRT) was the standard of care and neurosurgeons were consulted infrequently except in the case of large tumors causing a symptomatic mass effect and in cases where the primary diagnosis was unknown. In these situations, surgical resection was required to either improve a patient’s neurologic condition or provide a histologic diagnosis. However, this all changed in the 1990s when stereotactic radiosurgery (SRS) gained acceptance and the involvement of neurosurgeons in the care of this patient group increased exponentially. A number of randomized clinical trials have better defined the role of SRS in metastatic brain disease. It has been demonstrated that SRS improves local tumor control compared with WBRT alone (7), improves survival for patients with a single metastasis when given in addition to WBRT (1), and provides equivalent survival when used alone for patients with 1e4 tumors compared with patients having both SRS and WBRT (2). Most recently, Yamamoto et al. (11) from the Japanese Gamma Knife Society showed in the largest study to date (1194 patients) that survival in patients with 5e10 tumors having SRS alone was not inferior compared with patients with 2e4 tumors. It is recognized that the chance of new tumor formation is higher when SRS is performed alone (2, 6). However, many physicians and their patients choose to undergo SRS alone for brain metastases to eliminate the potential neurotoxicity that has been associated with WBRT (5). In summary, level 1 evidence supports using SRS alone as initial treatment for patients with as many as 10 brain metastases, with the qualification that this approach requires vigorous radiologic
Key words Gamma Knife radiosurgery - Nonesmall cell lung cancer - Single brain metastasis - Stereotactic radiosurgery - Surgical resection -
2
www.SCIENCEDIRECT.com
Abbreviations and Acronyms SRS: Stereotactic radiosurgery WBRT: Whole-brain radiation therapy
follow-up to detect intracranial progression requiring additional therapy. Despite the increasing use of SRS in managing many patients with brain metastases, there continues to be clear-cut indications for the surgical removal of these tumors. Resection of metastases generally permits the rapid withdrawal of corticosteroid therapy compared with SRS in patients with large tumors and provides a method of histologic confirmation. For patients with type 2 diabetes mellitus, corticosteroid therapy can make serum blood glucose control difficult, requiring conversion from oral agents to insulin injections; patients with type 1 diabetes mellitus are especially vulnerable to the medical complications associated with uncontrolled serum glucose levels. The overall care of patients with diabetes is much simpler with tumor removal than SRS, which often requires ongoing corticosteroid therapy for weeks to months after the procedure. Patients with hemorrhagic brain metastases, not uncommon with melanoma or renal cell carcinoma, are another instance in which open surgery is beneficial due to the rapid relief of the mass effect. Consequently, despite there being little debate about the best treatment for a patient with a single 5-cm frontal metastasis (surgical resection) or a patient with 5 small tumors including one located in the thalamus (SRS), there is a shortage of good information comparing these 2 techniques for patients with metastatic brain disease who are reasonable candidates for either approach. Bougie et al. (4) compared survival and local tumor control in 115 patients with nonesmall cell lung cancer with a single brain metastases managed with either resection (n ¼ 43) or SRS (n ¼ 72) between 2004 and 2011. Although patients were not
From the Departments of 1Neurological Surgery and 2Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA To whom correspondence should be addressed: Bruce E. Pollock, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 84, 1:2-3. http://dx.doi.org/10.1016/j.wneu.2015.03.057
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.03.057
PERSPECTIVES
randomized, there was no difference between the groups with regard to age, histology, tumor stage, performance status, or intent of treatment (curative versus palliative/supportive) of the primary disease. As expected, tumors in the resection group were larger. Also, most patients (91%) undergoing surgical resection received some form of postoperative radiation. No patient in the SRS group received WBRT as part of their initial management. Local tumor control was similar for the 2 groups (72% after resection versus 79% after SRS). Patients who underwent surgical resection survived longer (13.3 months versus 7.8 months), but aggressive treatment of the primary disease and metachronous presentation appeared to be the major factors associated with survival. They concluded that the survival advantage seen in patients who undergo surgical resection related mostly to the care of their primary disease, and patients who undergo SRS should achieve similar survival times if they also receive equally aggressive treatment of their nonesmall cell lung cancer. Determination of which patients with brain metastases benefit from tumor removal rather than SRS is difficult for a number of reasons. First, most studies to date on this topic have been retrospective, single-center series whose results are skewed by selection bias, a small number of patients, and poor follow-up
REFERENCES 1. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary J, Souhami L, Rotman M, Mehta MP, Curran WJ Jr: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363: 1665-1672, 2004. 2. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G: Stereotactic radiosurgery plus whole-brain radiation therapy vs. stereotactic radiosurgery alone for treatment of brain metastases. JAMA 295:2483-2491, 2006. 3. Bindal AK, Bindal RK, Hess KR, Shiu A, Hassenbusch SJ, Shi WM, Sawaya R: Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg 84:748-754, 1996. 4. Bougiea E, Masson-Côtéb L, Mathieu D: Comparison between surgical resection and stereotactic radiosurgery in patients with a single brain metastasis from non-small cell lung cancer. World Neurosurg 2015. 5. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS,
(3, 8, 10). Muacevic et al. (9) performed a randomized clinical trial comparing resection plus WBRT with SRS alone for patients with a single brain metastasis. Patients were aged between 18 and 80 years, had a Karnofsky Performance Status 70, stable systemic disease, and a single resectable tumor 3 cm. The primary end point of the study was survival. Although the trial was stopped prematurely due to poor patient accrual, analysis of the 64 randomized patients found no difference in survival, neurologic death rates, or local tumor control rates. Distant tumor progression was greater in the SRS alone group. They concluded that SRS alone was less invasive and had similar local tumor control rates compared with resection plus WBRT. It is unlikely that another randomized clinical trial will be performed on this topic. Second, this is a heterogeneous patient group with different pathologies, varying tumor size and location, and differing degrees of primary disease control, all of which influence survival. Third, although survival is a simple outcome measure, it is also the end point most susceptible to selection bias in retrospective comparisons. For comparison of focused tumor techniques such as resection and SRS, local control is more appropriate than survival from the time of treatment. Based on the available information, most patients with brain metastases will not require a craniotomy and can be effectively managed with SRS alone.
Maor MH, Meyers CA: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10: 1037-1044, 2009. 6. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann R, Carrie C, Hassel MB, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller R: Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29:134-141, 2010. 7. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC: Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427-434, 1999. 8. Muacevic A, Kreth FW, Horstmann GA, Schmid-Elsaesser R, Wowra B, Steiger HJ, Reulen HJ: Surgery and radiotherapy compared to gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg 91:35-43, 1999. 9. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW: Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the
WORLD NEUROSURGERY 84 [1]: 2-3, JULY 2015
brain: a randomized controlled multicentre phase III trial. J Neurooncol 87:299-307, 2008. 10. O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR: A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys 55:1169-1176, 2003. 11. Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K: Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15: 387-395, 2014.
Citation: World Neurosurg. (2015) 84, 1:2-3. http://dx.doi.org/10.1016/j.wneu.2015.03.057 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
3
To Remove or Not to Remove, that Is the Question? Bruce E. Pollock1,2
B
rain metastasis from nonesmall cell lung cancer is likely the most common brain tumor in adults because of the high prevalence of this disease. For many years, wholebrain radiation therapy (WBRT) was the standard of care and neurosurgeons were consulted infrequently except in the case of large tumors causing a symptomatic mass effect and in cases where the primary diagnosis was unknown. In these situations, surgical resection was required to either improve a patient’s neurologic condition or provide a histologic diagnosis. However, this all changed in the 1990s when stereotactic radiosurgery (SRS) gained acceptance and the involvement of neurosurgeons in the care of this patient group increased exponentially. A number of randomized clinical trials have better defined the role of SRS in metastatic brain disease. It has been demonstrated that SRS improves local tumor control compared with WBRT alone (7), improves survival for patients with a single metastasis when given in addition to WBRT (1), and provides equivalent survival when used alone for patients with 1e4 tumors compared with patients having both SRS and WBRT (2). Most recently, Yamamoto et al. (11) from the Japanese Gamma Knife Society showed in the largest study to date (1194 patients) that survival in patients with 5e10 tumors having SRS alone was not inferior compared with patients with 2e4 tumors. It is recognized that the chance of new tumor formation is higher when SRS is performed alone (2, 6). However, many physicians and their patients choose to undergo SRS alone for brain metastases to eliminate the potential neurotoxicity that has been associated with WBRT (5). In summary, level 1 evidence supports using SRS alone as initial treatment for patients with as many as 10 brain metastases, with the qualification that this approach requires vigorous radiologic
Key words Gamma Knife radiosurgery - Nonesmall cell lung cancer - Single brain metastasis - Stereotactic radiosurgery - Surgical resection -
2
www.SCIENCEDIRECT.com
Abbreviations and Acronyms SRS: Stereotactic radiosurgery WBRT: Whole-brain radiation therapy
follow-up to detect intracranial progression requiring additional therapy. Despite the increasing use of SRS in managing many patients with brain metastases, there continues to be clear-cut indications for the surgical removal of these tumors. Resection of metastases generally permits the rapid withdrawal of corticosteroid therapy compared with SRS in patients with large tumors and provides a method of histologic confirmation. For patients with type 2 diabetes mellitus, corticosteroid therapy can make serum blood glucose control difficult, requiring conversion from oral agents to insulin injections; patients with type 1 diabetes mellitus are especially vulnerable to the medical complications associated with uncontrolled serum glucose levels. The overall care of patients with diabetes is much simpler with tumor removal than SRS, which often requires ongoing corticosteroid therapy for weeks to months after the procedure. Patients with hemorrhagic brain metastases, not uncommon with melanoma or renal cell carcinoma, are another instance in which open surgery is beneficial due to the rapid relief of the mass effect. Consequently, despite there being little debate about the best treatment for a patient with a single 5-cm frontal metastasis (surgical resection) or a patient with 5 small tumors including one located in the thalamus (SRS), there is a shortage of good information comparing these 2 techniques for patients with metastatic brain disease who are reasonable candidates for either approach. Bougie et al. (4) compared survival and local tumor control in 115 patients with nonesmall cell lung cancer with a single brain metastases managed with either resection (n ¼ 43) or SRS (n ¼ 72) between 2004 and 2011. Although patients were not
From the Departments of 1Neurological Surgery and 2Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA To whom correspondence should be addressed: Bruce E. Pollock, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2015) 84, 1:2-3. http://dx.doi.org/10.1016/j.wneu.2015.03.057
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2015.03.057
PERSPECTIVES
randomized, there was no difference between the groups with regard to age, histology, tumor stage, performance status, or intent of treatment (curative versus palliative/supportive) of the primary disease. As expected, tumors in the resection group were larger. Also, most patients (91%) undergoing surgical resection received some form of postoperative radiation. No patient in the SRS group received WBRT as part of their initial management. Local tumor control was similar for the 2 groups (72% after resection versus 79% after SRS). Patients who underwent surgical resection survived longer (13.3 months versus 7.8 months), but aggressive treatment of the primary disease and metachronous presentation appeared to be the major factors associated with survival. They concluded that the survival advantage seen in patients who undergo surgical resection related mostly to the care of their primary disease, and patients who undergo SRS should achieve similar survival times if they also receive equally aggressive treatment of their nonesmall cell lung cancer. Determination of which patients with brain metastases benefit from tumor removal rather than SRS is difficult for a number of reasons. First, most studies to date on this topic have been retrospective, single-center series whose results are skewed by selection bias, a small number of patients, and poor follow-up
REFERENCES 1. Andrews DW, Scott CB, Sperduto PW, Flanders AE, Gaspar LE, Schell MC, Werner-Wasik M, Demas W, Ryu J, Bahary J, Souhami L, Rotman M, Mehta MP, Curran WJ Jr: Whole brain radiation therapy with or without stereotactic radiosurgery boost for patients with one to three brain metastases: phase III results of the RTOG 9508 randomised trial. Lancet 363: 1665-1672, 2004. 2. Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, Hatano K, Kenjyo M, Oya N, Hirota S, Shioura H, Kunieda E, Inomata T, Hayakawa K, Katoh N, Kobashi G: Stereotactic radiosurgery plus whole-brain radiation therapy vs. stereotactic radiosurgery alone for treatment of brain metastases. JAMA 295:2483-2491, 2006. 3. Bindal AK, Bindal RK, Hess KR, Shiu A, Hassenbusch SJ, Shi WM, Sawaya R: Surgery versus radiosurgery in the treatment of brain metastasis. J Neurosurg 84:748-754, 1996. 4. Bougiea E, Masson-Côtéb L, Mathieu D: Comparison between surgical resection and stereotactic radiosurgery in patients with a single brain metastasis from non-small cell lung cancer. World Neurosurg 2015. 5. Chang EL, Wefel JS, Hess KR, Allen PK, Lang FF, Kornguth DG, Arbuckle RB, Swint JM, Shiu AS,
(3, 8, 10). Muacevic et al. (9) performed a randomized clinical trial comparing resection plus WBRT with SRS alone for patients with a single brain metastasis. Patients were aged between 18 and 80 years, had a Karnofsky Performance Status 70, stable systemic disease, and a single resectable tumor 3 cm. The primary end point of the study was survival. Although the trial was stopped prematurely due to poor patient accrual, analysis of the 64 randomized patients found no difference in survival, neurologic death rates, or local tumor control rates. Distant tumor progression was greater in the SRS alone group. They concluded that SRS alone was less invasive and had similar local tumor control rates compared with resection plus WBRT. It is unlikely that another randomized clinical trial will be performed on this topic. Second, this is a heterogeneous patient group with different pathologies, varying tumor size and location, and differing degrees of primary disease control, all of which influence survival. Third, although survival is a simple outcome measure, it is also the end point most susceptible to selection bias in retrospective comparisons. For comparison of focused tumor techniques such as resection and SRS, local control is more appropriate than survival from the time of treatment. Based on the available information, most patients with brain metastases will not require a craniotomy and can be effectively managed with SRS alone.
Maor MH, Meyers CA: Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10: 1037-1044, 2009. 6. Kocher M, Soffietti R, Abacioglu U, Villà S, Fauchon F, Baumert BG, Fariselli L, Tzuk-Shina T, Kortmann R, Carrie C, Hassel MB, Kouri M, Valeinis E, van den Berge D, Collette S, Collette L, Mueller R: Adjuvant whole-brain radiotherapy versus observation after radiosurgery or surgical resection of one to three cerebral metastases: results of the EORTC 22952-26001 study. J Clin Oncol 29:134-141, 2010. 7. Kondziolka D, Patel A, Lunsford LD, Kassam A, Flickinger JC: Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 45:427-434, 1999. 8. Muacevic A, Kreth FW, Horstmann GA, Schmid-Elsaesser R, Wowra B, Steiger HJ, Reulen HJ: Surgery and radiotherapy compared to gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. J Neurosurg 91:35-43, 1999. 9. Muacevic A, Wowra B, Siefert A, Tonn JC, Steiger HJ, Kreth FW: Microsurgery plus whole brain irradiation versus Gamma Knife surgery alone for treatment of single metastases to the
WORLD NEUROSURGERY 84 [1]: 2-3, JULY 2015
brain: a randomized controlled multicentre phase III trial. J Neurooncol 87:299-307, 2008. 10. O’Neill BP, Iturria NJ, Link MJ, Pollock BE, Ballman KV, O’Fallon JR: A comparison of surgical resection and stereotactic radiosurgery in the treatment of solitary brain metastases. Int J Radiat Oncol Biol Phys 55:1169-1176, 2003. 11. Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K: Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol 15: 387-395, 2014.
Citation: World Neurosurg. (2015) 84, 1:2-3. http://dx.doi.org/10.1016/j.wneu.2015.03.057 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2015 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
3
